Surgical procedures employing balloons and medical devices incorporating those balloons (i.e., balloon catheters) are becoming more common and routine. These procedures, such as angioplasty procedures, are conducted when it becomes necessary to expand or open narrow or obstructed openings in blood vessels and other passageways in the body to increase the flow through the obstructed areas. For example, in an angioplasty procedure, a dilatation balloon catheter is used to enlarge or open an occluded blood vessel which is partially restricted or obstructed due to the existence of a hardened stenosis or buildup within the vessel. This procedure requires that a balloon catheter be inserted into the patient's body and positioned within the vessel so that the balloon, when inflated, will dilate the site of the obstruction or stenosis so that the obstruction or stenosis is minimized, thereby resulting in increased blood flow through the vessel. Often, however, a stenosis requires treatment with multiple balloon inflations. Additionally, many times there are multiple stenoses within the same vessel or artery. Such conditions require that either the same dilatation balloon must be subjected to repeated inflations, or that multiple dilatation balloons must be used to treat an individual stenosis or the multiple stenoses within the same vessel or artery. Additionally, balloons and medical devices incorporating those balloons may also be used to administer drugs to a patient.
Traditionally, the balloons available to physicians were classified as either "compliant" or "noncompliant". This classification is based upon the operating characteristics of the individual balloon, which in turn depended upon the process used in forming the balloon, as well as the material used in the balloon forming process. Both types of balloons provide advantageous qualities which were not available from the other.
A balloon which is classified as "noncompliant" is characterized by the balloon's inability to grow or expand appreciably beyond its rated or nominal diameter. "Noncompliant" balloons are referred to as having minimal distensibility. In balloons currently known in the art (e.g., polyethylene terephthalate), this minimal distensibility results from the strength and rigidity of the molecular chains which make up the base polymer, as well as the orientation and structure of those chains resulting from the balloon formation process. The strength resulting from this highly oriented structure is so great that when the balloon is subjected typical inflation or operating pressures (i.e., about 70 psi to over 200 psi), it will not be stressed above the yield point of the polymeric material.
The yield point of a material is defined as the stress at which the individual molecular chains move in relation to one another such that when the pressure or stress is relieved, there is permanent deformation of the structure. When a material is subjected to pressure or stress below its yield point, the material will consistently follow the same stress-strain curve when subjected to multiple cycles of applying and relieving the stress or pressure. A material which exhibits the ability to follow the same stress-strain curve during the repeated application and relief of stress is defined as being elastic and as having a high degree of elastic stress response. This elastic behavior is highly desirable in balloons in order to ensure consistent and predictable balloon sizing regardless of the balloon's previous inflation history.
A balloon which is referred to as being "compliant" is characterized by the balloon's ability to grow or expand beyond its nominal or rated diameter. In balloons currently known in the art (e.g., polyethylene, polyvinylchloride), the balloon's "compliant" nature or distensibility results from the chemical structure of the polymeric material used in the formation of the balloon, as well as the balloon forming process. These polymeric materials have a relatively low yield point. Thus, the inflation pressures used in dilation procedures are typically above the yield point of the materials used to form distensible balloons. A distensible or "compliant" balloon when inflated to normal operating pressures, which are greater than the polymeric material's yield point, is subjected to stress sufficient to permanently realign the individual molecular chains of the polymeric material. The realignment of individual polymer chains permits the balloon to expand beyond its nominal or rated diameter. However, since this realignment is permanent, the balloon will not follow its original stress-strain curve on subsequent inflation-deflation cycles. Therefore, the balloon balloon upon subsequent inflations, will achieve diameters which are greater than the diameters which were originally obtained at any given pressure during the course of the balloon's initial inflation.
The term "elastic", as it is used in connection with this invention, refers only to the ability of a material to follow the same stress-strain curve upon the multiple applications of stress. See Beer, F. et al., Mechanics of Materials (McGraw-Hill Book Company 1981), pp. 39-40. Elasticity, however, is not necessarily a function of how distensible a material is. It is possible to have an elastic, non-distensible material or a non-elastic, distensible material. This is best illustrated in FIGS. 1, 2 and 3.
FIG. 1 represents an elastic, essentially non-distensible material. If this material was used to form a balloon, the balloon would be considered non-distensible because there is very little change in strain (diameter) as the stress applied is increased (inflation pressure). The balloon would be elastic because it follows essentially the same stress-strain (pressure-diameter) curve with the second application of stress (inflation).
FIG. 2 represents an elastic, distensible material. If this material was used to form a balloon, the balloon would be considered distensible because there is significant change in strain (diameter) as the stress applied is increased (inflation pressure). The balloon would be considered elastic because it follows essentially the same stress-strain (pressure-diameter) curve with the second application of stress (inflation).
FIG. 3 represents an inelastic, distensible material. Like FIG. 2, FIG. 3 shows a significant change in strain (diameter) and would therefore be considered a distensible balloon material. Unlike FIGS. 1 and 2, however, the same stress-strain (pressure-diameter) curve is not maintained upon the second application of stress (inflation).
It has been found that the optimal size of a dilatation balloon is about 0.9 to about 1.3 the size of the vessel being treated. See Nichols et at., Importance of Balloon Size in Coronary Angioplasty, J. American College of Cardiology, Vol. 13, 1094 (1989). If an undersized balloon is used, there is a high incidence of significant residual stenosis and a greater need for subsequent dilatation procedures. However, if an oversized balloon is used, there is an increased chance of coronary dissection. Therefore, physicians desire to use a balloon which will closely approximate the size of the occluded vessel or obstructed cavity being treated.
Because physiological vessels such as arteries are generally tapered, the nominal or rated diameter of balloons commercially available often do not correspond to the size of the vessel being treated. Physicians, therefore, are often faced with the prospect of using an undersized "compliant" balloon which can be expanded beyond its nominal or rated diameter, or an oversized "noncompliant" balloon which will follow the same stress-strain curve during multiple inflations (i.e., is elastic). Thus, physicians can choose from two general types of balloons depending upon whether they require a balloon which grows beyond nominal diameter. They may choose a "noncompliant" balloon if they require a relatively high strength balloon which will not expand much beyond its nominal or rated diameter, or a "compliant" balloon if they require a balloon which is capable of expanding considerably beyond the normal or rated diameter. As will be shown below, each of these properties is advantageous. However, it would be desirable to have to have a "compliant" or distensible balloon which also has the elastic stress response of a "noncompliant" balloon, as well as sufficient strength to be used in dilatation procedures.
Because physicians using a dilatation balloon do not know prior to the procedure what inflation pressures will be required to dilate a given obstruction or stenosis, it is desirable that the balloon being used have strength capable of withstanding the high inflation pressures typically associated with these procedures (i.e., about 70 to over 200 psi). A high strength dilatation balloon, which is capable of withstanding increased inflation pressure, is safer to use since the chances of the balloon bursting during the procedure are minimized.
Strength of a balloon is typically quantified by calculating the balloon's wall tensile strength. The overall strength of a balloon can be increased by increasing the balloon's wall thickness. As the wall thickness is increased, the balloon is capable of withstanding higher inflation pressures. However, as the wall thickness of the balloon is increased, the folded profile of the balloon, as well as the balloon's flexibility, may be adversely affected.
The relationship between the ultimate strength of the balloon, the inflation pressure which the balloon can withstand and the balloon's wall thickness is determined by the well known membrane equation: ##EQU1##
Depending upon the material used to form the balloon, the nominal, or rated diameter is achieved typically when the balloon is inflated between to about 5 bars to about 8 bars. The burst pressure is determined at 37.degree. C.
Since balloons, particularly dilatation balloons, must have the ability to traverse the confines of the obstructed areas to be treated, it is desirable to have a balloon which has a narrow folded profile. This "profile" represents the smallest opening through which the balloon, in its deflated state, may pass. The profile of the balloon depends in large part upon the wall thickness of the finished balloon (i.e., the sterilized dilatation balloon product). Therefore, it is desirable for a finished balloon product to have a folded profile which is as narrow as possible, particularly if the balloon is to be used in an angioplasty procedure.
Another important characteristic of balloons in general, and more specifically dilatation balloons, is the distensibility of the finished balloon product. Distensibility, also referred to as percent of radial expansion, is typically determined by comparing the nominal or rated diameter of the balloon with the diameter at some arbitrarily selected higher pressure (e.g., 10 bars). The distensibility or percent radial expansion is calculated using the following formula with all measurements taking place at about 37.degree. C.: ##EQU2## For example, balloons made of polyethylene terephthalate have a low distensibility (i.e., less than about 5% at 200 psi). See for example U.S. Pat. Nos. 32,983 and 33,561 to Levy which discloses balloons formed from polyethylene terephthalate and other polymeric materials.
It is also desirable that the balloon be elastic or have a high degree of elastic stress response. Elasticity, which also can be referred to as the repeatability of a balloon, is characterized by the ability of the balloon to consistently follow the same stress-strain curve after being subjected to multiple inflations to normal operating or inflation pressures (i.e., about 10 bars or greater). That is, a balloon which has a high degree of elastic stress response will retain the same diameter-pressure relationship and will consistently obtain the same diameter at the same pressure during repeated inflation-deflation cycles. Balloons which have poor elasticity or a low degree of elastic stress response have a tendency to "creep" or "deform" after multiple inflations and fail to return to their nominal or rated diameters after being subjected to multiple inflations at increased pressures.
A dilatation balloon which has a high degree of elastic stress response is particularly desirable when a physician is treating multiple stenoses within the same artery. If the balloon is "inelastic", after the first stenosis is dilated at an increased pressure, the physician would not know what the balloon's "new" starting diameter is prior to attempting to dilate subsequent stenoses. If the physician fails to correctly guess the balloon's "new" diameter prior to beginning treatment of another stenosis there is an increased risk of oversizing the balloon which could result in coronary artery dissection or other damage to the vessel. Therefore, to ensure the patient's safety, some physicians elect to remove the balloon catheter from the patient and reintroduce a new sterile balloon catheter prior to attempting to dilate subsequent stenosis within the same vessel. However, this is time-consuming and undesirable for the patient. Additionally, the cost of the individual balloon catheters prohibits the use of multiple balloon catheters when treating multiple stenoses within the same vessel. Thus, to minimize the chance of oversizing the balloon when treating multiple stenoses within the same vessel, a physician may attempt to use a dilatation balloon which is noncompliant. However, as discussed previously, because such a balloon will permit little expansion beyond the balloon's rated or nominal diameter, the physician may not have available a balloon of sufficient size to safely treat the other stenoses within the same vessel.
Elastic stress response is determined by inflating a balloon to 5 bars at about 37.degree. C. and measuring the balloon's diameter. The balloon is then inflated to a pressure of 10 bars in about 20 seconds and held for an additional 20 seconds at 37.degree. C. The balloon's diameter is then measured. The internal pressure of the balloon is then decreased to 5 bars and the "new" 5 bar diameter of the balloons is determined. For this invention, the elastic stress response or repeatability is calculated using the following equation: ##EQU3##
A balloon with maximum or complete elastic stress response permits the balloon, after being inflated to a pressure of 10 bars, to return to the same diameter it had at 5 bars prior to the inflation to the higher pressure. Such a balloon would have maximum repeatability, or an elastic stress response of 0.00. As the repeatability of the balloon decreases, the elastic stress response decreases and, as defined above, numerically becomes greater than 0.00. For example, balloons formed from polyolefin copolymers in the art have poor repeatability and a relatively low degree of elastic stress response and have a numerical elastic stress response of about 9.
It would be particularly desirable if a "compliant" balloon was able to possess an adequate degree of distensibility so that the balloon could be inflated to correspond to the size of the vessel being treated, while at the same time being highly elastic to ensure repeatable sizing and a high degree of elastic stress response so that the physician would know the balloon's "new" diameter at all inflation pressures prior to attempting to dilate multiple stenoses within the same vessel. This enhanced combination of properties would allow physicians to conduct dilation procedures in a safer manner in arteries where the physician requires balloon sizing not conveniently provided by "noncompliant" balloon products currently available in the art.
Another desirable characteristic of a balloon is flexibility. Improved flexibility will permit a balloon to traverse, not only occluded arteries, but also other obstructed or narrow body cavities and openings resulting in minimal damage to the vessel or cavity through which the balloon catheter is being navigated.
A further desirable property of a dilatation balloon, is the optical clarity of the finished balloon product. Although the optical clarity will not adversely affect a balloon's overall ability to dilate a stenosis or obstruction, most physicians will not use a balloon which has a cloudy appearance. The optical characteristics of a balloon or balloon catheter, therefore, must be taken into account when forming a balloon.
While the foregoing properties are desirable in balloons, these attributes are typically adversely affected by the sterilization process which all balloons and balloon catheters must be subjected to prior to their use in the human body. For example, when a balloon in the art is exposed to the increased temperature and humidity of a traditional sterilization process (e.g., high humidity, temperature of about 50.degree.-60.degree. C., about 12% ethylene oxide and about 88% Freon.TM. for approximately 12-16 hours) the balloon tends to shrink which causes a corresponding increase in wall thickness. Moreover, this increase in wall thickness will adversely affect the folded profile of the sterilized balloon product. Furthermore, the distensibility of many balloons is adversely affected by the sterilization processes currently used in the art. Therefore, it is also desirable that the sterilization process used to treat balloons and balloon catheters provide adequate sterilization while at the same time not adversely affecting the physical characteristics of the finished balloon or balloon catheter product.
It has now been found that novel distensible balloons, particularly dilatation balloons, can be formed by processing a polymeric material composed of polymer chains having sufficient regions of molecular structure with inter-molecular chain interaction to ensure the integrity and strength of the structure, as well as sufficient regions which permit sections of the polymer chains to "uncoil" to permit growth. The balloons contemplated by this invention (i) are sufficiently distensible (i.e., about 5 to about 20%) to allow treatment of various sized arteries, (ii) have a high degree of elastic stress response (i.e., less than about 5.00) which permits the physician to treat multiple stenoses within the same artery without having to be concerned with increasing balloon diameter after repeated inflations and (iii) have strength sufficient to treat hardened stenoses (i.e., greater than about 14,000 psi). The balloons formed using the process of this invention will have an overall advantageous combination of these physical properties i.e., distensibility, elastic stress response and tensile strength, superior to those exhibited by the "compliant" balloons currently available. It has also been found that these enhanced properties will not be adversely affected by subjecting the balloons and balloon catheters formed following the method or process of this invention to a novel sterilization process. This novel balloon forming process and novel sterilization process can be used regardless of whether the balloon is coated.